22-17629002-T-C

Position:

• chr22-17629002-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000399782(BCL2L13):​c.-653T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 316,570 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (86 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (13 hom.)
• Consequence: BCL2L13 ENST00000399782 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.469

Genes affected

BCL2L13 (HGNC:17164): (BCL2 like 13) This gene encodes a mitochondrially-localized protein with conserved B-cell lymphoma 2 homology motifs. Overexpression of the encoded protein results in apoptosis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

BCL2L13 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 22-17629002-T-C is Benign according to our data. Variant chr22-17629002-T-C is described in ClinVar as [Benign]. Clinvar id is 1253201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L13	XM_047441286.1	c.-596T>C		5_prime_UTR_variant	1/7		XP_047297242.1
BCL2L13	XM_047441290.1	c.-653T>C		5_prime_UTR_variant	1/7		XP_047297246.1
BCL2L13	XM_011546119.2	c.-593+96T>C		intron_variant			XP_011544421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L13	ENST00000399782	c.-653T>C		5_prime_UTR_variant	1/7	1		ENSP00000382682.1
BCL2L13	ENST00000399781.5	n.52+96T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2891 AN: 152160 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00352 AC: 578 AN: 164292 Hom.: 13 Cov.: 0 AF XY: 0.00290 AC XY: 253 AN XY: 87328

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.00706

Gnomad4 ASJ exome AF: 0.00410

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000279

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000517

Gnomad4 OTH exome AF: 0.00612

GnomAD4 genome AF: 0.0190 AC: 2899 AN: 152278 Hom.: 86 Cov.: 32 AF XY: 0.0185 AC XY: 1374 AN XY: 74458

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0165 Hom.: 6

Bravo AF: 0.0223

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73876479; hg19: chr22-18111768;